Search Results (490)

In regenerative medicine, orthobiologics, particularly platelet-rich plasma (PRP), are widely used due to their ability to enhance natural tissue repair mechanisms. PRP contains a concentrated pool of growth factors and cytokines that enhance regeneration while also acting as a biomimetic scaffold, thereby optimizing the microenvironment for tissue healing. In bone tissue engineering, PRP is commonly combined with synthetic or natural biomaterials, as its fibrin matrix alone lacks sufficient mechanical stability. However, even such composite systems frequently exhibit limited osteoinductive capacity, necessitating further supplementation with bioactive components. This review evaluates the regenerative potential of PRP in bone defect healing when combined with osteoinductive agents in preclinical in vivo models. We present compelling experimental evidence supporting the efficacy of this combined therapeutic approach. Full article

Sim, a potent HMG-CoA reductase inhibitor, exhibits notable anabolic effects on bone and can upregulate osteogenic genes such as BMP-2, thereby promoting bone formation. An ideal drug delivery system for Sim involves its controlled and sustained release at the defect site to minimize adverse side effects. In this study, Sim was first modified via HP-γ-CD to form a hydrophilic Sim/HP-γ-CD inclusion complex, thereby improving drug solubility and dispersion in aqueous systems. A gelatin–sodium alginate (Gel/SA) hydrogel was then employed as the drug delivery matrix to construct a Gel-SA-Sim/HP-γ-CD hydrogel sustained release system. This hydrogel system exhibited a high water content (82%), along with enhanced mechanical properties, including a compressive strength of 0.284 MPa and a compressive modulus of 0.277 MPa, suggesting strong load-bearing capacity and favorable stiffness. Importantly, Sim was released in a controlled and sustained manner over 7 days, without exhibiting burst release behavior. In vitro osteogenic differentiation assays demonstrated that optimal concentrations of Sim effectively enhanced cellular bioactivity and osteoinductive performance, offering a promising approach to enhance the bioactivity, osteogenesis, and osseointegration of orthopedic implants. Full article

This review article provides a comprehensive evaluation of Infuse^® and InductOs^®, two ground-breaking recombinant human Bone Morphogenetic Protein-2 (rhBMP-2)-based bone graft products, focusing on their tissue-level regenerative responses, clinical applications, and associated costs. Preclinical and clinical studies demonstrate that rhBMP-2 induces strong osteoinductive activity, effectively promoting mesenchymal stem cell differentiation and vascularized bone remodeling. While generally well-tolerated, these osteoinductive effects are dose-dependent, and excessive dosing or off-label use may result in adverse outcomes, such as ectopic bone formation or soft tissue inflammation. Histological and imaging analyses in craniofacial, orthopedic, and spinal fusion models confirm significant bone regeneration, positioning rhBMP-2 as a viable alternative to autologous grafts. Notably, advances in delivery systems and scaffold design have enhanced the stability, bioavailability, and targeted release of rhBMP-2, leading to improved fusion rates and reduced healing times in selected patient populations. These innovations, alongside its proven regenerative efficacy, underscore its potential to expand treatment options in cases where autografts are limited or unsuitable. However, the high initial cost, primarily driven by rhBMP-2, remains a critical limitation. Although some studies suggest overall treatment costs might be comparable to autografts when factoring in reduced complications and operative time, autografts often remain more cost-effective. Infuse^® has not substantially reduced the cost of bone regeneration and presents additional safety concerns due to the rapid (burst) release of growth factors and limited mechanical scaffold support. Despite representing a significant advancement in synthetic bone grafting, further innovation is essential to overcome limitations related to cost, mechanical properties, and controlled growth factor delivery. Full article

Background/Objectives: Hydrogels have emerged as strategic biomaterials in bone tissue engineering, especially in the peri-implant context, due to their high biocompatibility, water retention capacity, three-dimensional defect filling, and ability to mimic the extracellular matrix. These properties allow physical support for regeneration and the incorporation and controlled release of bioactive, immunomodulatory, and osteoinductive agents. Methods: This narrative review aimed to summarize recent advances in developing and applying hydrogels for the repair of peri-implant bone defects. The selection of studies was performed in PubMed, Web of Science, and EBSCO databases, covering the period from 2010 to 2025. Thus, 14 preclinical and clinical studies were included in this review. Results and Conclusions: Hydrogels show great potential for peri-implant bone regeneration due to their biocompatibility and ability to deliver bioactive agents. While preclinical results are promising, clinical validation remains limited. Further studies are needed to confirm their efficacy and ensure the safe translation of these findings into clinical practice. Full article

Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by the addition of bone morphogenetic protein-2 (BMP-2) or amorphous calcium phosphate granules with strontium ions (Sr-ACP), in order to improve the clinical regeneration of subchondral bone, still incomplete. Methodology: Normal human osteoblasts (NHOsts) were seeded on the scaffolds and grown for 14 days in the presence of human osteoclasts and conditioned medium of human endothelial cells. NHOst adhesion and morphology were observed with transmission electron microscopy, and metabolic activity was tested by Alamar blue assay. The expression of osteoblast- and osteoclast-typical markers was evaluated by RT-PCR on scaffolds modified by enrichment with BPM-2 or Sr-ACP, as well as on unmodified material used as a control. Results: NHOsts adhered well to all types of scaffolds, maintained their typical morphology, and secreted abundant extracellular matrix. On the modified materials, COL1A1, SPARC, SPP1, and BGLAP were more expressed than on the unmodified ones, showing the highest expression in the presence of BMP-2. On Sr-ACP-enriched scaffolds, NHOsts had a lower proliferation rate and a lower expression of RUNX2, SP7, and ALPL compared to the other materials. The modified scaffolds, particularly the one containing Sr-ACP, increased the expression of the osteoclasts’ typical markers and decreased the OPG/RANKL ratio. Both types of scaffold modification were able to increase the osteoinductivity with respect to the original scaffold used in clinical practice. BMP-2 modification seemed to be more slightly oriented to sustain NHOst activity, and Sr-ACP seemed to be more slightly oriented to sustain the osteoclast activity. These could provide a concerted action toward better regeneration of the entire osteochondral unit. Full article

Osteoporosis compromises bone quality and impairs implant osseointegration. Since an adequate bone bed is essential for implant stability and success, this study evaluated the effects of implant surface functionalization with zoledronic acid (ZOL), alone or combined with ruterpy (TERPY), on peri-implant bone healing in healthy (SHAM) and osteoporotic (OVX) rats. ZOL has antiresorptive properties, while TERPY exhibits osteoinductive potential. The hypothesis was that ZOL + TERPY would act synergistically by inhibiting bone resorption and promoting new bone formation. Sixty-six female Wistar rats (3 months old) were divided into six groups (n = 11) according to systemic condition (SHAM or OVX) and implant type: conventional (CONV), ZOL, or ZOL + TERPY. Surgeries (sham or bilateral ovariectomy) were performed on day 0, and implants were placed in the tibial metaphysis on day 90. Fluorochromes were administered on days 104 (calcein) and 114 (alizarin), and euthanasia was performed on day 118. Samples were analyzed histologically via confocal microscopy and micro-computed tomography (Micro-CT). The ZOL + TERPY groups demonstrated significantly accelerated peri-implant bone repair, showing greater bone formation and organization; improved BV/TV, Tb.N, and I.S.; and reduced Tb.Sp and Po.Tot compared to CONV and ZOL-alone groups. In conclusion, ZOL + TERPY enhances and speeds bone healing, even under osteoporotic conditions. Full article

In this study, a shape-changeable 3D scaffold with photothermal effects was developed to address the clinical challenges of complex bone defects. The multifunctional construct was fabricated via in situ polymerization combined with a gas foaming technique, creating hierarchical porous architectures that mimic the native bone extracellular matrix. By incorporating polydopamine (PDA)-modified amorphous calcium phosphate (CA) into poly(propylene glycol) (PPG)- and poly(ԑ-caprolactone) (PCL)-based polyurethane (PU). The obtained scaffolds achieved osteoinductive potential for bone tissue engineering. The surface PDA modification of CA enabled efficient photothermal shape conversion under near-infrared (NIR) irradiation, facilitating non-invasive remote control of localized hyperthermia. The optimized scaffolds exhibited interconnected porosity (approximately 70%) with osteoconductive pore channels (200–500 μm), resulting in good osteoinduction in cell culture, and precise shape-memory recovery at physiological temperatures (~40 °C) under NIR for minimally invasive delivery. The synergistic effect of osteogenesis promotion and photothermal transition demonstrated this programmable scaffold as a promising solution for integrated minimally invasive bone repair and defect reconstruction. Full article

Staphylococcus species are often the cause of implant-related infections, posing a significant clinical challenge in orthopedics. Antimicrobial peptides (AMPs) like LL-37-derived FK-16 and GF-17 offer promising alternatives to conventional antibiotics; however, they require suitable delivery systems to overcome rapid degradation. The aim of this study was to develop and evaluate silk fibroin (SF) and osteoinductive peptide-enriched silk fibroin (PSF) sponges that can be used locally for FK-16 and GF-17 delivery. Two concentrations of FK-16 or GF-17 were loaded into SF and PSF sponges. Swelling behavior and AMP release profiles were analyzed for 72 h. Time-kill assays were conducted on MRSE and MRSA clinical strains to assess antimicrobial activity. FK-16 released quickly (>90% within 24 h) and then maintained a stable plateau from both SF and PSF matrices, which was associated with bactericidal activity against MRSE strains. In contrast, the release efficiency of GF-17 was lower and did not achieve significant antimicrobial effects. Neither peptide exhibited effective activity against MRSA under the tested conditions. PSF sponges showed higher swelling and enhanced FK-16-mediated antibacterial performance compared to SF counterparts. FK-16-loaded PSF sponges are a promising biomaterial for treating local orthopedic infections related to MRSE. The findings underscore the significance of peptide–matrix interactions in determining therapeutic outcomes and suggest the need for more in vivo evaluation of AMP-functionalized PSF scaffolds. Full article

Background: Bone loss management is a tough challenge in orthopedic and trauma surgery that is generally treated using graft or substitute. Bone is the second most common transplanted tissue behind blood. Autologous bone graft represents the gold standard, while allograft is generally used as a secondary option, considering their impressive osteoconductive and osteoinductive properties. However, both allograft and autograft sources are limited. Therefore, synthetic bone substitutes gained popularity due to their low cost and ease of application. β-tri-Calcium phosphate (β-TCP) is a promising material implemented as a bone substitute. One of the limits of bone substitutes is related to their three-dimensional organization, which rarely replicates that of the normal bone. b.Bone™ is a novel bone substitute derived from rattan wood with a unique 3D structure that mimics the architecture of the human bone. This study aims to objectively evaluate the osteointegration of b.Bone™ in complex clinical settings. Methods: We retrospectively evaluated eight patients who underwent surgeries requiring filling bone loss through the use of b.Bone™. Osteointegration of the bone substitute was evaluated radiologically using a modified Van Hemert classification. Results: Eight patients were enrolled into this study: five females and three males with a mean age of 53,75 years old. b.Bone™ was applied in the following shapes: granules in four cases, cylinders in three cases and a prism in one. In four patients, the osteointegration reached a grade Van Hemert 4, three a grade 3, and only one a grade 2. Conclusions: β-TCP-based bone substitutes, such as those derived from rattan, appear to facilitate successful osteointegration in various clinical settings. Future studies with larger cohorts and longer follow-ups are necessary to evaluate the long-term efficacy of this promising substitute. Full article

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

The aim of this review is to investigate the possibility of fabricating coatings functionalized with bioactive molecules. These coatings are interesting when applied to biomedical devices, particularly in the orthopedic field. In fact, the application of calcium phosphate-based coatings on the surface of implanted devices is an effective strategy to increase their osteoinductive and osseointegrative properties. Several coating fabrication technologies are presented, including chemical deposition and physical methods. The application of bioactive molecules in combination with calcium phosphate coatings may improve their osteointegrative, antibacterial, and antitumor properties, therefore increasing the performance of implantable devices. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article